Arthritis, an inflammatory disease of the joint, occurs in various forms such as rheumatoid arthritis and related diseases with joint inflammation.
Rheumatoid arthritis, also called chronic rheumatism, in particular, is a chronic multiple arthritis characterized by inflammatory changes in the synovial membrane of the articular capsule inner layer. Arthritic diseases like rheumatoid arthritis are progressive and cause joint disorders such as deformation and acampsia, often resulting in severe physical disorder due to lack of effective treatment and subsequent deterioration.
Traditionally, these forms of arthritis have been chemotherapeutically treated with various agents, including steroids such as cortisone and other adrenocortical hormones, non-steroidal anti-inflammatory agents such as aspirin, piroxicam and indomethacin, gold agents such as aurothiomalate, antirheumatic agents such as chloroquine preparations and D-penicillamine, anti-gout agents such as colchicine, and immunosuppressors such as cyclophosphamide, azathioprine, methotrexate and levamisole.
However, these drugs have drawbacks such as severe adverse reactions, adverse reactions hampering the drug's long-term use, lack of sufficient efficacy and a failure to be effective against already-occurring arthritis.
Accordingly, there is need for the development of a drug which exhibits excellent prophylactic/therapeutic action on arthritis, with low toxicity in clinical situations.
Traditionally, various compounds have been synthesized as quinoline or quinazoline derivatives. Known compounds having an aminomethyl group at the 2-position of a 4-phenylquinoline or 4-phenylquinazoline skeleton include the 2-dimethylaminomethyl derivative and 2-morpholinomethyl derivative described in Synthesis, Vol. 9, p. 718 (1979), and the 2-alkylaminomethylquinoline derivative described in the Farmaco, Vol. 44, 555 (1989). However, there is no disclosure of any compound wherein the 2-position of a 4-phenylquinoline or 4-phenylquinazoline skeleton is bound to a nitrogen atom of a nitrogen-containing unsaturated heterocyclic ring via an alkylene group as in the present invention.